In the late 1950's a new drug was launched in Europe. Clinical trials weren't like they are today; as a result, thousands of children suffered from extreme birth defects or died before birth due to Thalidomide. Frances Kelsey, a new FDA reviewer, pushed for safety data before allowing it to be approved US, and spared the US from tragedy.
We are joined by Neil Vargesson, Chair in Developmental Biology and expert in Thalidomide, as we discuss the drug's history and how it caused birth defects. Justine Peterson, P.A., joins us also to give a clinical perspective on drugs, trials, and how they shape her world.
In the late 1950's a new drug was launched in Europe. Clinical trials weren't like they are today; as a result, thousands of children suffered from extreme birth defects or died before birth due to Thalidomide. Frances Kelsey, a new FDA reviewer, pushed for safety data before allowing it to be approved US, and spared the US from tragedy.
We are joined by Neil Vargesson, Chair in Developmental Biology and expert in Thalidomide, as we discuss the drug's history and how it caused birth defects. Justine Peterson, P.A., joins us also to give a clinical perspective on drugs, trials, and how they shape her world.
The President's press conference from the new State Department Auditorium in Washington DC August 1 1962. At noon, I have several announcements. Recent events in this country and abroad, concerning the effects of a new sedative called thalidomide emphasize again, the urgency of providing additional protection to American consumers from harmful or worthless drug products. United States has the best and the most effective Food and Drug Law of any country in the world. And the alert work of our Food and Drug Administration, and particularly Dr. Francis calci, prevented this particular drug from being distributed commercially in this country. Nevertheless, the drug was given to many patients on an investigational basis. We are reviewing what steps can be taken administratively to make this stage in the future, less dangerous. We have recommended a 25% increase in the Food and Drug Administration staff, the largest single increase in the agency's history, and the full amount was voted today by the countries of the Congress. And it is clear that to prevent even more serious disasters from occurring in this country in the future, additional legislative safeguards are necessary.
Diane Cox:Hi, I'm Aaron Harmon. And I'm Diane Cox Welcome to Inside Out quality.
Aaron Harmon:both Diane and I build and implement quality systems in the biotech and medical device industry. But we often get asked, Is this really necessary? That we know if we are doing too much too early? Or do we even need a quality system?
Diane Cox:Our goal is to explore questions like these real life events and experiences shared by our guests from various regulated industries. We will show you why quality is not just about compliance and how when it's done right, it can help your product and company improve lives and make a difference.
Aaron Harmon:What you just heard was President Kennedy announcing one of the most impactful pieces of legislation which shaped our modern day FDA, the Kefauver Harris amendment of 1962 the US dodged a major catastrophe thanks to Francis Kelsey, a lady who followed her husband to teach Pharmacology at the University of South Dakota. She was later recruited to join the FDA as a reviewer and her first assignment was an application for some sleeping pills as they were referred to. The application was expected to be an easy approval done in a few months. While studying the application. She read a report from a London medical journal suspecting the drug thalidomide caused peripheral neuropathy. So she persisted in demanding data to prove the drug was safe. The data wasn't there, and she didn't back down from pressure to approve it. As a result, the US was spared a massive medical disaster. President Kennedy later awarded her the President's Award for Distinguished federal civilian service
Unknown:resident the honor of presenting Dr. Francis O Kelsey, medical officer Food and Drug Administration Department of Health, Education and Welfare, and she is accompanied by the Secretary of that department. The Honorable Anthony J. celebrancy. Dr. Kelsey, are exceptional judgment and evaluating a new drug for safety for human use, as prevented a major tragedy of birth deformities in the United States. Through high ability and steadfast confidence in her professional decision. She made an outstanding contribution to the protection of the health of the American people. I know that we're all most indebted to Dr. Kelsey, the relationship the hopes that all of us have for our children, I think indicates how I'm sure to Dr. Kelsey, how important her work is and those who labor with her to protect our families. So doctor, I know that you know how much the company appreciate what you've done.
Aaron Harmon:solidified ushered a law into effect in the US requiring clinical evidence of safety. There is much more to thalidomide though it's complicated from a biological and chemical aspect, medical aspect and social and ethical aspects. The impact was not in the US primarily, but mainly in Europe, also in Canada, Japan and Australasia, where it was initially distributed as a sedative, and soon after for morning sickness. On the show with us today we have Dr. Neil Varga son professor and one of the world's leading experts in thalidomide. And it's pharmacology. He is the chair in Developmental Biology at the University of Aberdeen. Welcome to the show, Neil.
Neil Vargesson:Thank you very much. It's it's nice to be here. And thank you for the invitation to come along today.
Aaron Harmon:Now, it's great to have you on the show. So the first question to dive into this, what drew you to study thalidomide?
Neil Vargesson:Yeah, this is a this is a topic very close to my heart. And anyone that knows me knows I'm very OCD about bout it. I've known about it all my life, I've grew up with friends or family friends. And one of those family friends was a thalidomide survivor, no arms and very short legs. And so as a child, I was fascinated by it. But it was really about 20 years ago when I'm a developmental biologist and I study limb development. And I'm particularly interested in how blood vessels allow limbs to grow from the embryo out and how you get five fingers. And why you don't have six fingers and why you why you have two arms and two legs, and not four arms and four legs, for example. You know, one of the big things about limb development is we don't know how birth defects or limb defects come about, and solidified is the gold standard, right? It's it's, it was the biggest teratogenic event of the 20th century, probably ever, causing a wide range of birth defects, particularly to limbs and limbs, or the stereo tipic picture in people's heads of what thalidomide did to people. And so I got back into it about 20 years ago, because I was interested in in, could we work out how thalidomide affected the limbs and the body. And if we could understand that, could that allow us to understand a bit more about normal limb development, and then help us understand about other birth defects. My view was, if we understood how thalidomide worked, then this would help us understand normal development, but would also tell us about the drug about making safer forms of the drug, but also tell us a little bit about how drugs impact on embryos. And so that was at the same time, there'd been a revolution in genetics and in pharmacology. And you know, you were able to pharmacologically break the drug down and start to really question which bits of the drug caused the birth defects and start to nail down what bit the drug is the bad bit and what bit the drug is the good bit from that you could then do advanced molecular biology and advanced imaging and actually study for the first time how the drug actually works in an embryo and what is it actually doing? And how does it cause the damage. And that's what got me back into studying it. It was advances in molecular biology and in developmental biology, but also this long term interest I've had, as to how that drug caused such severe damage to the embryo, but particularly to the limbs because I'm a limb development biologist. And I always go back to when I give lectures to my students at the university, how did that might cause limb defects. And so that it was that it was it was just a combination of the interest, my research going really well on limb development and starting to want to know how limb defects come about. And then the advances in molecular biology, pharmacology allowed us to really start to do some really nice experiments to show how thalidomide worked. And that's that's basically what we did. One quick
Aaron Harmon:question for clarity Treta genic, that would be something that causes birth defects.
Neil Vargesson:teratogenic is an exogenous substance, that is not naturally found in the body that is taken by someone that causes a birth defect. So a drug, a pesticide, a medicine, heavy metals, such as if you drinking water has got LED in it, for example, which some places do that's, that's, that's a Trojan, because it's not naturally found in the body. And it causes a birth defect. Yeah.
Diane Cox:from a biological perspective. And through your studies, why did Thalidomide cause birth defects.
Neil Vargesson:So it took us quite a bit of time to look at this. Now, you have to remember that this drug itself was withdrawn in Europe in the end of 1961. After there were reports from Australia, and from Germany, independently of each other, I might add, indicating that this drug was the cause of these birth defects. And it was shown that women that were pregnant, and who had taken the drug, had the babies with the damage and women that didn't take the drug had normal babies. So it was these two studies by Billiken lens in Germany and by Bill McBride in Australia. That was the eye opening time. And that was when the drug was withdrawn. And up to that point, there was loads of theories about what was going on. And it was scaring people because you had this really, really severe birth defects which are very rare. I mean, you know, limb reduction deformities, where you have a you have your your arms or your legs, and they're incredibly short than they should be incredibly rare. And so to see 1000s of children in Europe and around the world have these problems. were scaring people. And there was all sorts of theories that it was, you know, due to pollution from several world wars in Europe and around the world. It was fallout from the atomic, the atomic bombs used in World War Two, all sorts of weird and wonderful theories. But it was it was, so it was Billiken lens in 1961 and Bill McBride in Australia in 1961. That showed it was solidified. So ever since then, there's been lots of theories and proposals put forward as to how thalidomide causes birth defects and is over 30 different theories. And these range from affecting DNA directly causing mutations to affect in the nervous system to affecting blood vessels to causing cell death to affect in the bones directly. And depends on your viewpoint. And if you wish to find a paper that says, it's definitely this theory, you'll find that and if you find another, you'll find another paper that say, says that it isn't that theory because of this. And so what I think that the opinions were in the 1990s, or, or the late 1990s, early 2000s, was there was a view that it was the nerves were involved. And that was the prevailing ideas. And I was interested in understanding a bit more about that I was interested, as a limb developmental biologist, how does it How does the effect of a nerve cause such a severe defect like folk Amelia, folk, Amelia is where you have the reduction, or loss of the long bones in your arms and legs. So either your upper arm, the humerus is very short, or it's missing, and the radius and owner in your forearm is short or missing, and you have your digits coming out of your shoulder blades. So I was interested in you know, a little bit in, well, what role did the nerves then have in limb development. So what we did was, we took the drug and, and with a very, very good colleague and collaborator, Doug Figg, who works at the National Cancer Institute in the National Institutes of Health in Bethesda, on the east coast. He's a pharmacologist. And what we did was, he had worked out ways to break the drug down and make different analogues. And as you know, for that the mind has multiple actions in the body, it has actions on the blood vessels, it has actions on your inflammatory system, and it has actions on your immune system. And it also has actions on the, on the nervous system. And it was originally devised to be a sedative. So it was supposed to reduce the activity of the nervous system to calm people down. And since then, it's been shown to have all these different actions. So it's got lots of different actions. And the question that we had was, which one of those actions is causing the birth defects? We know that if you put the whole molecule on to an embryo, it causes damage, but I was interested in which of those actions or is it all those actions that caused the problems. And so Doug, Doug fig, is a pharmacologist, as I mentioned, and he had broken the drug down and made different analogs, which had different actions. And some of the some of the actions of the analogs were just on the blood vessels. Some of them were on the inflammatory system, and some of them had all the actions. And so what we did was we put it onto onto embryos, chicken embryos, and we found that you got birth defects, particularly limb defects and spinal defects, but you only got it if you blocked blood vessel formation. And so we, we found those back in 2009, that it was the action of the drug on the blood vessels in the embryo that's causing the birth defects. And you can, you know, famously solidify works in a time sensitive window, where early in development, if you take the drug, you get more damage the earlier in development, then later, so if you take it, let's say week four, or five, because the embryo is forming at that time, and the limbs are all forming as the internal organs, there's much more damage than if you took it, say, week six, or seven, when most those tissues are fully formed. So we can demonstrate that in the embryos. We showed that in 2009. And since then, we've been, we've spent most of our time looking at how thalidomide affects blood vessels. And we recently published work showing that it can do it rapidly. And it can do it via some molecular signaling molecules that were recently identified as solidified binding partners. But it can also do it independently of those. And so it suggests that flutamide has multiple actions on the embryo, but the key damage comes about by the antagonism or the loss of the blood vessels. And so what you can imagine, is, as the blood vessels are forming in the embryo, they're growing through the embryo to allow the tissues to get oxygen and nutrients. But if you stop that process, by this drug, then you're going to the tissues going to die off or not form. And that's how we think the limb defects come about is because at the time that the the embryo was exposed to the drug, it was the limbs were growing out, it needed its blood vessels, and then you've got the vessels being prevented from forming, the tissue can't grow out, and you either lose the tissue, or the tissue just can't grow the way it should. And by the time the drug has worn off, and the vessels can go back, you've then got your tissue damage. We've demonstrated that in several different studies. So that was the stuff we did and that was a few years ago. We also showed that actually, if you block nerves and you inhibit nerves, in the in the forming limbs, they don't cause limb defects. So the old theory that If it was the nerves causing the problem was a nice theory. And it's a theory that really inspired people, including myself to study the drug again. But it turns out not to be quite right. And it looks like in fact, what's going on. Because the nerves actually follow the blood vessels into the limbs or into tissues later in development, they're not the first ones to go in the vessels are, it looks like the vessels caused the damage, the nerves then try to grow in, and they make the damage even worse. So they're not directly causing it, but they are making it worse if you like. And then recently, there's been some molecular studies that have identified molecular targets, one of one of which is called cerebral and this is a molecule that's involved in removing functions of other genes that are no longer required in development. So if you think about an embryo, and you think about all the different molecular signals that are required to make one, at some point, you need to lose those molecular signals when you're when they've done their job, right. And the way you do that is you have a molecule like Sarah blonde, which then tags those molecules for destruction. And it was shown about 2010 That thalidomide bind Sarah blonde. And since then, this, this interaction is shown to be quite valid to explain thalidomide actions in adults. So when you give the lid amide, to people to treat leprosy, for example, or multiple myeloma, we know that it's doing it via an interaction with Sarah blonde. But actually, does that work in the embryo? Are there some recent studies that say that third might combine Sarah bond and it can down regulate some genes in the embryo, which could cause some of the thalidomide damage? And we've recently shown in it's a paper that came out this year that the lid amide does seem to bind Sarah blonde in blood vessels, but he can also do it independently of cerebral and so it would appear, where we're at the moment his blood vessels are involved, cell death is involved, Sarah bond is involved, but there's likely to be more molecular targets as well. So in a nutshell, that's that's how it causes the birth defects. I would say it's due to preventing blood vessels growing through the embryo. And if you prevent that, you then get tissue loss and the damage to the tissue. But what's the molecular target? What is the actual target that says the vessel shouldn't grow? That's probably Sarah blonde and other targets.
Diane Cox:So Neil, one, one question that's going through my mind is, I mean, all of these studies sound like they have been in the 90s, the 2000s, can you put into context for us? When did the potential problems start getting reported on thalidomide? And how long was that happening?
Neil Vargesson:Yeah, it was a weird time. So birth, the children were being born with birth defects in Europe, from about 19. I think the first report case was Christmas Day 1956. And that was to a lady who was married to an employee of the company that made the drug and their baby was born with, I think they had no ear lobes. And it was at the time was just put down to one of those things. It was not until after 1961, I believe that it was then linked that third of my quarters, those problems, and this is the problem, because trying to prove whether a drug does or does not cause birth defects is incredibly hard. And you have to do lots of different studies. And yeah, it takes time to work it out. The the manufacturers, they said that they did all the testing that was needed in that era, which is a very different era to us, of course, I guess the question I have or still have is, that's fine. That might be the case. But when did they actually know that there was a link to birth defects? Did they know earlier than then when it was withdrawn in November 30 1961. In the UK, or did they not know at all. And it wasn't until after this, that it became apparent that when you screened it in a variety of animal species, it causes birth defects. So it wasn't until after it was withdrawn that we knew. And it was in the 1960s. So it was shown to be effective, or causing problems in chickens, non human primates, and some other species. And incredibly, it was found to not be very sensitive in mice, and rodents. Now, that's very, very pertinent, because in those days, most animal testing was done on rodents. And so the lid amide turns out to be one of the first drugs identified to be species specific in its action, that it doesn't really affect mice, but it's incredibly damaging to humans. And so of course, if you're testing things in one species, and one species only happens to be a mouse, and it turns out that that drug isn't effective in mice, you're going to miss the fact that it's a potential teratogen right. And this is what Francis Kelsey then led, she led the way if you like in changing the way that we test our drugs, which we which we still follow today. She She laid the groundwork, her papers in 1968, for example, and before then, really changed the way we test our drugs and now you have to have Multiple animal species, you have to have several preclinical trials and then clinical trials, just like we've gone through with the vaccine for COVID, for example, lots of different things to check that it is safe. And it's so it took the thalidomide disaster to change the way we test our drugs. And we haven't had disasters quite like that. Since it's not completely infallible, there have been some issues, but it works. It tests the drugs. But it took it took until the mid 60s To know that it was really causing problems in animal embryos. And then there was a big gap several decades, where there was very little research done on it. It was then found in 1994, to be antiangiogenic. And what I mean by that is it it stops blood vessel formation. And a very nice paper by Robert D'Amato and Judah Folkman showed that very nicely that it stops blood vessel formation. And so that's why it became a drug to be used for anti cancer treatment. And it still is tested today. And it was also shown in 1965, would you believe just a few years after it was originally withdrawn, that it was effective against leprosy. The legend goes that a male patient with leprosy or complications of leprosy, which is a very nasty bacterial infection, which damages nerve endings in the skin, and causes horrible inflammatory lesions, I went to see a GP in Israel. And this Israeli GP or physician had some thalidomide knew it was a sedative, and it was anti inflammatory so gave him some and the legend goes that this patient recovered within a few weeks. And now we know that thermite is used to treat leprosy in some parts of the world, including Brazil. So it again, it took a bit of time for people to understand, um, how that the drug does that. But in the last sort of 1015 years, loads of work has been done to understand how to the mind is, is anti inflammatory, how it affects blood vessels. And more and more research is being done on how it causes Tourette agenesis, or, or birth defects. More work has been done, if I'm honest on on its clinical applications in adults. So leprosy and anti inflammatory disorders then has been in birth defects. But it's changing the last few years, we've seen quite a few papers come out and including my own work, but also other people's work looking at Sarah blonde, and how Sarah blonde might be, might be causing birth defects. So it did take some time. And if I'm honest, if I'm, if I'm brutally honest, we still don't know the complete mechanism of how this drug works, even though it's been 60 years since it caused its first damage. And this is due to its complexity. I mean, this drug is quite unique, really, I mean, it has the ability to affect blood vessels, your inflammatory response, your immune response, it can be used to treat cancers. It's even being tested to treat COVID-19 right now. So you can see that it's got this remarkable range of activities. And this might explain why it's, it's taken so long to understand how the drug acts because it's got these multiple ways of behaving in the body.
Aaron Harmon:We've talked a lot about the biology, but what about the broader impact in Europe when it was first being used. And then the years following.
Neil Vargesson:Thalidomide was marketed around the world in 46 Different countries by 1961. And it was called different names in different countries. So in Germany, it was called counter gun. In Britain, it was called disavow. And it was called different names in other parts of the world, in Japan and elsewhere. It was it was not officially released in the United States. And that's because of Francis Kelsey and her bravery and extraordinary Scientific and medical progress. And I still, I tell my undergraduate students that I think she's one of the most underrated scientists of the 20th century, because she stopped for sure she stopped a major disaster in United States. If she'd licensed that drug, um, the drug would have gone to hundreds of 1000s of people who knows what, what the impact would have been. But there are survivors in the United States. There were clinical trials done in the early 60s. And so there are there are a number of people in America that are affected by this drug, and they're still trying to get recognition to this day. The impact in Europe was the drug was withdrawn in, in Britain in end of November 1961, and around the world in 1962. And the scandal that it caused, you know, changed the way that we test our drugs, right. I mean, this this led to public fury. I should also point out that the drug companies at that point, the distributor in the United Kingdom was distillers company who make alcoholic products, and they refused to pay compensation initially. But ultimately, ultimately, they did and it it did it through public power. And what I mean by that is a massive campaign was set up by a journalist working for the Sunday Times. And I forgotten his name here. I'm
Aaron Harmon:terrible, isn't it? This person? Yes.
Neil Vargesson:How old Howard Evans? That's right. So Howard Evans found out about these thalidomide children and was horrified that they had been damaged by a drug that this company had distributed. And it wasn't clear at the time, whether it was safe, it wasn't clear what testing had been done, the drug companies were very quiet about it. And so he instigated a campaign to to the public, and ask them not to buy any of the products of that company. And they made things like gin, whiskey, you name it, then they pretty much made everything. And it worked. And they lost a lot of custom in the 1970s. I even have the adverts for it here at home. And it worked. Their company then paid out compensation and they still are today, and distillers are part of Diageo. And they still pay compensation to the UK survived today. So that worked, it was a great example of a fantastic journalism and public power. So that was the implication of the thalidomide disaster. The poor children were then taken to various hospitals and looked after and they weren't experimented on, but that they were then, you know, given prosthetic limbs to try to make them look more normal. And this cause issues for these these kids. And it was bad enough anyway, where you've got a birth defect, but you can imagine how society treated them in the 1960s. And that was across Europe. And today, they're in their late 50s, early 60s. And they have a group and they are integrate into society, you've got some of them are famous actors, some are going to politics, and society is definitely changed. But in that era, it was not a nice time. But it certainly changed our perspective on disability and on truck safety. And again, with Francis Kelsey, in the US, the UK and other authorities in Europe, then then put in drug safety laws, which changed the way drugs are checked and made safe.
Diane Cox:From a legal perspective, was there any thought that this was potentially a scandal by the drug makers, in that they may be knew that this was unsafe and cause these problems but still kept selling?
Neil Vargesson:There is a lot of debate about what was known at the time and what wasn't known, and what was tested and what was not tested. And I have to be honest, testing of drugs in that era, is not what it is today, that didn't really appear to be any sort of strict regulations either. And so I honestly don't know what was done and what was not done the drug company claim they did everything that was needed to be done. Michael, my question is, when did they know it was causing birth defects. And I don't know if they, if they know that themselves. But that's more pertinent to me, it may well be that the test they did before the drug was on the market seemed to make it safe, because as I mentioned, it doesn't really affect mice very much. And if you were only testing in adult animals, you're not going to see birth defects. What the New Drug Regulations did was made sure that you test drugs, on pregnant species as well. So there's that complication to it. And then there is the complication of when did they know and i That, to me is a more interesting point. And we're never going to know the answer to that. I think whether it was a cover up i I can't comment on that. Sure. That's all right. Don't get me in trouble.
Diane Cox:Understandable. Yeah.
Neil Vargesson:It did change. If it wasn't solidified, there was going to be another drug that caused a similar disaster, because the drug testing in that era was not, is not done the way it is today. So I do think it was more like you just took out animals, you gave them a dose of the drug. And then if they if they survive, then it's safe. And you know, very little was known about how drugs are metabolized and how they broke down. We didn't know at that time that some drugs could cross the placenta and go directly to the embryo. So there were concerns about that. But, you know, thalidomide changed all that. And it made us open our eyes to the fact that actually most stuff go go through the placenta and into the embryo. And it was Francis Kelsey, that changed the way we do this. So if it hadn't been solidified, if if that drug had never gone in the market, it was only going to be another couple of years before another drug came out that cause similar problems. So it was it was an accident waiting to happen, if you like.
Diane Cox:Yeah, I totally agree.
Aaron Harmon:So in terms of the drug development, Now, you mentioned it's being used for leprosy and for cancer, as I
Neil Vargesson:mentioned earlier, so in 1965, it was shown by a doctor in Israel that it could, it could be useful to treat leprosy, or complications of leprosy. And now it is now it's used in Brazil, particularly in Brazil, and some other parts of Equatorial parts of the world to treat complications of leprosy and it's really effective. I mean, within six weeks of having these horrible lesions, six weeks treatment through the mind gets rid of those lesions. So it's very effective. Unfortunately, there there is new, there is a new generation of thalidomide babies or two In Brazil, because unfortunately, the drug is not as tightly regulated as it is in Europe and the US. And so if there's a, there's a medicine, sharing culture in Brazil, so, you know, hospitals are very, very far away from the villages where these people have got leprosy. They take days to get to the hospital, they get their meds, and they go back to their village. And to save somebody else going, they just give them some medicine. They don't know any different. So we do have a new generation of children being born in Brazil. And this is another reason why I got interested, by the way, in when you see pictures in 1996 of children with thalidomide, embryo apathy, you're thinking, what, what's going on? What Why, why do we still have this? And so that was another reason why I got interested in this sort of so well, how does this why is this happening? And more importantly, if the drug is that effective to treat leprosy? Is there a way that we can dissect out the good bits, the bits of the drug that treat leprosy, but we'll lose the bits that caused the birth defect. And I think we have done that now. Because the new research that we're doing, we have identified versions of thalidomide with Doug figure, National Cancer Institute in the NIH, we've identified versions of the drug that appear to be perfect for inflammatory illnesses like leprosy. And they don't have and we got versions that do that, but they don't cause blood vessel loss, and they don't cause birth defects. So long term we make, we may have a new version of the drug that we might be able to use, that could be used to treat leprosy and leprosy only. And if it was taken by someone by mistake, who was pregnant, it shouldn't cause a birth defect. That's it, that's a good thing. And that should have mentioned that at the start that that's another reason why I got into this because seeing children in 1996, on TV with birth defects caused by thalidomide is something I'd never see again. So that that got me sort of kind of wince upset, but it reminded me of my interest in lithium ion. And because we were looking at limbs at the time, it made me more interested, and the changes in the molecular biology and pharmacology, it was perfect time to study it. And we've we've done all that. So it's used for leprosy. It's also used to, in clinical trials, for some cancers, it's very useful to treat early onset cancers like prostate cancer, that's before a tumor gets, it gets to a certain size, it needs to get blood vessels, then once it's got blood vessels, it can get to any size at once. So if you can get a cancer early, and you can get it solidified, then you can stop the cancer or the tumor, getting the blood vessels, you stop it growing. So it's in trials for that. As I mentioned, it's also recently been shown to be what is certainly in clinical trials to treat COVID-19 lung inflammation and pneumonia. It was used to treat swine flu, what 10 years ago, and it's used to treat a whole host of other conditions such as multiple myeloma, which is a white blood cell cancer. And in fact, it's so good to treat myeloma that it prolongs patients lives by 18 months. So it's a very effective drug for those conditions. And it's also used to treat some leukemias, as well as arthritis as well. So it's got a whole host of things, it's useful. And there's also another very interesting condition. It's been shown for in 2010, which is something called H H t, which is called hereditary hemorrhagic. Tell injector Sia, and this is a very nasty condition affecting young people, where arteries and veins in your body merge, and they form and they hemorrhage, basically, they die. It's very nasty. And thalidomide was shown in 2010, to be quite effective for that to treat HHT. So it's got lots of different uses, and more uses are being found each year. So it is a really remarkable drug. And it's it's up there with aspirin for the things that it can do. It's it's used for so many different things. But it is incredibly dangerous as well. So now in the US and in Europe and other parts of the world, there are procedures in place to ensure that people taking it are not pregnant, that they're using several forms of contraception, that they have regular pregnancy tests to ensure that we don't see any more thalidomide children. And that that hasn't happened in Europe or the US since the 19th. or anywhere else apart from Brazil and a few other places since the 1960s. So, you know, if it's taken safely, then it's safe. But you need to make sure that there is a regulated set of procedures to make sure that patients don't take it when they want to they take it when they have to take it and that there are Princey tests and contraceptives in place to prevent pregnancy.
Diane Cox:I had no idea of the wide range of use of the drug. I only knew of a couple I guess safe I've heard of it being used to treat some cancers and leprosy but other than that, that was that was the extent of it. Very interesting.
Aaron Harmon:Yeah. That's a great story for pharmacology. Oh, yeah.
Neil Vargesson:The amazing drug. I guess there is rumor. I mean, I don't I don't put much weight in this, but there was rumor that it was devised in World War Two by Nazi scientists, but I mean, I just can't see how you would make a sedative during World War Two, but But yeah, so it was, I think the pattern for it is 1954. And it was released in 57. And it was in it was in the UK and 58 until 61. But its origins before then are a mystery. And the reason why there's this theory behind it is because the company that made it did hire former scientists from Nazi Germany. So I guess if you, if you do that any company that does that, everyone's going to think that there's some nasty, nasty origin of a drug. But there's no evidence for that. But that that will have that if you do a Google search on thalidomide, and the war you'll you'll see reports that there might be a link to it. But some whether that's the case or not, we just don't know. But the bigger picture is yes, that this drug is being used for more and more things. And this year, particularly with COVID-19, as an alternative to before we had the vaccines or the the possibility of vaccines, there was an awful lot of looking at drugs that are used for other conditions, and then read arriving them for COVID. And deliver mide has been in a clinical trial in Japan in the US, I believe, to see if it would be effective to relieve the symptoms of COVID. And from what I've seen, it does appear to be a very effective, so new new things every year. Yeah,
Aaron Harmon:I think it's great that it wasn't abandoned, that the restore research going on to to be able to ferret out the other uses for it
Diane Cox:and wonder drunk otherwise.
Neil Vargesson:Yeah, I mean, I think the survivors have a very different view of it, I think they would like to see it banned, for obvious reasons. But now, if you tell someone with multiple myeloma or with complications of leprosy that you can no longer take that drug, they will be very upset with you because it's very, very effective. But it was surreptitious, it was a it was an accident that the drug was found to be useful for leprosy, right? I mean, a patient goes to a physician's clinic with these horrible lesions. And the doctor says, Well, I've got some thalidomide on my shelf, he shouldn't still have had it, he should have got rid of it. But he still had it. He knew that it was a very effective anti inflammatory, gave it to the male patient, just thinking, well, what's the worst it's going to happen here? And it worked. That's amazing that that's like, you know, that's one of those eureka moments in science and medicine, right? Where you say, Well, that's what a great result. And it was that that's that's, that really led the renascence of the drug, because further testing in the 1990s showed that it was affecting the blood vessels. So it could be used for cancer. So that that's really where it came from. But I think today, if you said a drug was not safe, you would drop it, you would never go back to it. So just a different era, and a different way of doing things. But wonder drug is yes, I guess you could call it that, given what it can do. But it's I don't think you'll ever get away from from what it did in the 1960s
Aaron Harmon:when he said that he said earlier weird in wonderful for theories. So I think it could be a weird and wonderful drug.
Neil Vargesson:Yeah. And I guess I should also be honest, I mean, every time we think we've worked out how this drug works, and we think we've nailed it, it does something that just reminds you that? No, we haven't. So when I started this work, was nearly 20 years ago, I thought we'd have this solved in five years, six years. And I have more questions today than I had then. So that tells you how, how complex the drug is, and the many different things that it can do. And the potential for this drug is amazing. But again, we we still don't understand the complete mechanism of how this works. We know quite a bit more about it, and how it works in myeloma and in leprosy in the adult than we do for birth defects. And that's for obvious reasons, because very few people study its actions on birth defects, because it's no longer used in pregnant people. But for our group, you know, we want it to see well, how does it cause birth defects, but then can you make a form of the drug that keeps the good bits and doesn't cause birth defects. So if you like personalized medicine, so you take a drug for a specific condition, then it does exactly what it says on the tin, you know, it treats leprosy or it treats multiple myeloma, it doesn't do anything else. And that's, that's one of the goals that we have. And that's the goal of several other labs in the world looking at this drug right now to try and make it safe. But our view was that you had to go back to the embryo to, to understand how it works properly, because the actions in the embryo and the actions in the adult are very likely to be very different, because they're different body systems, right? The embryo is growing, and all these cells are moving around and you've got all these different molecular signals. And a drug going into that environment is going to cause different things than it would in an adult where you're not growing and you've got stabilized structures and things. So that was our ethos for going back to the embryo that most research in the last sort of 20 years has been done in the adult to look at other conditions that it can be used to treat very successfully. But we were always at the view that how did it cause those birth defects and and can you ever? Can you if you can understand that then that would help us understand developmental biology. And that's, I think that's what it's done. But we're still not 100% certain of of the precise mechanism that's going to take another. Well, hopefully not too long, but hopefully before I retire, but um, but who knows, I thought this would take five years, and so far it's taken 20. So that's science for you. It's, it's, it's it's frustrating, but wonderful at the same time. It's like a puzzle. Yes, exactly. Right. It's a puzzle. I think, to be honest, we probably do have all the bits and pieces that we need all the bits of information that we need to put it together. So it's like a jigsaw puzzle, we just need to get the right order now. But it that's going to still take time. And you know, to be honest with you, there's there's not much funding in drugs that cause birth defects, right? Because most of the funders say, Well, we know it's causing birth defects. So we just don't give it to people that are pregnant. Problem solved, which is completely understandable in a society where we've got other things to worry about, like COVID-19, and viruses that kill people. So you know, we, I get the priorities. And that's why it's taking so long because folks like myself, we're using other sources of funding to help us get this research funded and stuff. So we'll get
Diane Cox:there. Neil, this was just absolutely fascinating. And thank you so much for being on the show. We really appreciate it.
Neil Vargesson:Thank you, Neil. My pleasure,
Aaron Harmon:anytime. Now we'll take a quick break to hear from one of our sponsors.
Unknown:Today's startups become tomorrow's growth engines. In South Dakota, we're entering a new stage of expansion for a biotech industry, and you'll want to be part of it. Hi, I'm Tony Johnson, Executive Director of South Dakota biotech, where the state affiliate of the International bio organization and we're proud to be leading a state that's driving innovation to feed, fuel and heal the world. South Dakota biotech is here to inform, to connect, and to advocate for our critical industry. Whether you're directly involved in biotechnology, or looking to learn more about it, we want to hear from you. Find us at www that SD bio.org. Now back to the show.
Aaron Harmon:Following up on our interview with Neil, Diane, and I have Justine Peterson, Pa in town with us. Years ago, I worked with Justine in the lab, she went on to pursue medicine and we were able to sneak some of her time to have her join us today. Welcome to the show, Justine.
Unknown:Thanks, Aaron and Diane for having me here today.
Aaron Harmon:So it was everyone's initial thoughts of the Interview with Neil,
Diane Cox:just absolutely fascinating stuff that he had to say I learned so much on this episode.
Unknown:Yeah, I agree with that. I listened to it last night and was kind of amazed at how much had to go in, and how much research they've done since then to try to continue on with possibility of this medication, maybe in some other place for it in medicine somehow, in a safer realm.
Aaron Harmon:When I think about drug development, I kind of envision there like being some kind of curtain. On the one side you have drug development process. And then on the other you have the customers, patients, physicians, those that are administering these drugs. And that curtain is essentially controlled by the FDA. So on the one side of the curtain, how much exposure and adjusting withdrawals pa do you have to the drug development process,
Unknown:you have very little from the provider end of things, I just feel like that's a really expensive curtain. And so not until the drug companies have put in lots and lots and lots of money, do I get a little peek behind the curtain to say, hey, we might have something promising coming,
Aaron Harmon:listening to the whole story of thalidomide and the potential disaster what did happen in Europe and played out, it felt like at the time there really wasn't occurred. And it was drug developers making drugs and saying here, just go try this and see if it works well for you. And what we've done because of that disaster is built up a structure of drug development, you have safety tests that occur, you look at the risk, you look at the benefit, it then goes to the FDA, and then from there, it then goes to the other side. And so you're getting something with the expectation that it is going to be at least more beneficial than risky to your patients.
Unknown:Yeah, that's correct. I think it still makes it hard for patients to trust medicine, which is kind of unfortunate. A part of that process with the FDA, is that in those studies, they quite frankly, have to record every single like reported side effect, and not so that's why you'll see with like almost every medicine like most common side effects, you know, nausea, fatigue, diarrhea, vomiting, those kinds of things, because they're just the most, you know, normal constitutional symptoms. And so patients get really weirded out because they see this big long insert that you see on drugs like it could cause all these symptoms or side effects and that makes patients really nervous about wanting to take them but that is the side effect of having all these extra checks and balances.
Aaron Harmon:But the nice thing is you have access to that were in the early 1960s Before this act was put in place. As a physician, you may have no visibility to what could even occur after it was given to a patient.
Unknown:Yeah, absolutely. At the tip of my fingers. I have some How many like pharmacology resources when a patient comes in to say, Well, I'm having this side effect or that side effect? I mean, I can go down to like, you know, one to 2% range of, yes, it happened in research in this percentage of the population. So it's possible that it could be that medicine that's causing this issue that you're now having. So it's been quite helpful at times.
Aaron Harmon:Now, with clinical trials that occurred with the lid amide. We're giving it to physicians and saying, Here you go use this and see what happens. From a quality stance. Dan, is that what happens now?
Diane Cox:Oh, man, we get in big trouble if that's what happened? No, no, absolutely not. There's a whole process and regulations around how to conduct clinical studies. And there's a lot that goes into it, there's a, you know, entire protocol that needs to be reviewed and approved by the FDA. And not only by them, but by individual hospitals, that of performing the studies, there is all kinds of consent, that has to be given by the patients and the physicians, all kinds of stuff, all sorts of controls that go in to even beginning to have a clinical study on a particular drug. And in my case, devices,
Aaron Harmon:Francis calcium is stated in a paper, it has occasionally been stated that the present laws and regulations will result in fewer new drugs. Certainly new drugs, whether certifiable or not, will have to undergo rigorous evaluation, but no more rigorous than what should have occurred in the absence of any federal law. And so my read on that was simply that there's an expectation as a drug developer, to generate something that you have the information about the risks, the side effects, the benefits, and what harm may cause from that. And it's a scientific obligation, not just a regulatory obligation, that we should be doing that automatically. Because ultimately, our goal is to get medications and devices out to help people.
Unknown:I do think it's probably limiting to some extent, or at least drawing that process out significantly longer than maybe in the past. But it's definitely a necessity. I mean, I think if you're thinking about well, do I want to give this medicine to my loved one? Or would I give it to my you know, you you want that kind of warm, fuzzy feeling to say, hey, it's gone through 25,000 other people's hands and bodies before it's gotten to me. So it's an absolute necessity, and probably should have been implemented long before.
Diane Cox:Right? Yeah. Yeah, making it a personal situation makes makes you kind of think, you know, from an ethical standpoint, and just your personal relationship with a particular individual who might be receiving a drug under study or a brand new drug, I would absolutely want that to go through the rigorous process that it requires today. Unless something has been proven in one application, the side effects have been well understood for some time, and now they're expanding the application. In those cases, I feel like it could be a little bit different, and how much testing might need to go in. But when it's a brand new drug being used as a first indication, yeah, I would, I would want that to be rigorously tested.
Aaron Harmon:I have a class that I teach occasionally. And in there, I'll draw out a triangle. And I put quality on the top, and then the bottom left, I put speed to market and on the right, I put cost to market. And so thinking of that from drug development, if you are dying from a cancer as an example, and there's no product in the market, and someone says, Hey, we have something in development, but we're trying to meet rigorous quality controls, we're trying to make sure you have all the data in place, before we get that the patients and is probably going to take another five years, then our concern about speed may change. That's true, if the drug is going to go fast, and it's going to have that high quality bar. But now it's going to cost a million dollars for treatment, I may then have a different feeling again. So in the class, I draw this triangle, I asked people, How would you rate your need for that quality part? Knowing that speed and cost are other factors? And how important is it for you getting a drug? Some folks are right up on the top because they don't want anything that would harm them. Where others were much lower, because you're like, hey, I'll take risk. I would rather have it be cheap take on the risk. And if something goes wrong, and then it does, but so there is a very individualistic view, I think, yeah, but I feel like with something like the Linamar The FDA has put a line and said no more can you go below this bar. There is now a level of an a battery of studies you have to do to actually be good enough for us to now release you out to the public because the risk to the public is much more impactful than a few individuals.
Unknown:And even despite that, I mean we still get drugs that are pulled from the market on occasion. It doesn't happen frequently. But they've trickled in over the probably last 30 years. There have been a few here and there that they've determined But we kind of made a mistake that probably wasn't the best drug and pull it off. And there's plenty of drugs that are approved here that aren't approved in other countries. So we don't always share opinions on that
Aaron Harmon:system, maybe more applicable to the general medical device in biotech industries is with when someone's bringing a new drug to market, it's like first time and you ask him, Who is this going to be for? They will say, everyone, like this can be for young it can be for old, we think it can help everyone. And my view of it is, you should pare it down to a very small group, because your clinical trials are much more defined, and your chance of getting it through or quicker than saying, Okay, now we're going to include pregnant women, now we're going to include pediatrics, we're going to have kids within this range because of growth development. And if you try to do everything at once the cost is so immense, versus just a small subset and then expand that out as you have.
Diane Cox:Yeah, I mean, even from a credibility standpoint, if you take if you start with a smaller scope, a smaller indication or population, and you expand from there, that's from the outside looking, and that's a really good, it's a better strategy to start small and expand from there. When you start larger, and you have a larger population, and you have to scale back from there. To me, that's not a great strategy, because from from the population standpoint, that just makes you look like you haven't done your homework properly,
Aaron Harmon:solidified that flutamide started out broad, wider, yeah, and then got pared back and now is being used for small subsets of people. Right, if
Diane Cox:they would have started there. Do you know is that how they're kind of drug companies? Are they? Are they kind of taking that approach lately? Where they start with a smaller scope? I know they want to go larger. But do you find in practice that they kind of skim drugs?
Unknown:Yeah, so and maybe not the best for that, because I normally only deal with adults in my practice. But I would say, most of the time, things get marketed, I think as adults primarily, unless it's it's specific targeted medication for a pediatric reason, or for an obstetric reason. Mainly because ethically, it's hard to find pregnant women and children to enroll into studies and have like decent at num enough numbers to actually prove efficacy and such. So I think it's usually more marketed just to general population, like adults per se, for that reason of just not being able to find participants.
Diane Cox:But that's a good point. Every I'm just having kids of my own every label that I read, I mean, you see six and under attended under ask a physician or do not do not give to six and under or attended under? Yeah, so it's, it seems to be very much just we don't know what would happen. So it's at your own risk that you would give this medication.
Aaron Harmon:Thalidomide is now being understood what does it the mechanism of action is being figured out now, way many years after trying to launch out to market where modern day develop drug development, you are learning all those mechanisms before you go into the clinical trials. And that was also true with TGN 1412. Where it was not fully characterized. The results of that was the safety issues during the trial.
Unknown:Yeah, interesting flipside to some of this is, we have some medicines that have now been approved. And as they've been out, for instance, some of like the diabetes medications, they're great for lowering blood sugars. And as they've been out over the last five years or so they've now gotten new indications for reduced risk for like cardiovascular outcomes and things like that. So, you know, some of that is like, we've got these drugs, they've gone through all this rigorous, even though they went through all that they didn't even know what they were really, actually achieving. And now we're getting more data. And they're saying, Oh, well, these are actually good for this, too. So it's kind of nice that they started more when you're talking about starting a little bit more narrow. And now they're kind of broadening their focus and saying, hey, you know, we have, you know, the indication for this to the FDA now to as they've gotten done some of their longevity trials. That's yeah, kind of a bonus to what we do now and how we run them through these rigorous testing. Right.
Aaron Harmon:So Justin, what are your expectations from drug makers in terms of providing new safety and efficacy information?
Unknown:Yes, I think transparency would be the best thing I bless their hearts with the pharmaceutical representatives will come in and sell your drug to all these great things about it. And then, you know, think about like eight little asterisks at the bottom to say, oh, but and I really want them to, you know, be a little bit more transparent about the possibilities of adverse effects because there's some of these little nuances that are really important, depending on your patient. And I'd say most providers, or at least an internal medicine world that encompasses a whole lot of pharmacology. I mean, we're talking everything you're pretty much responsible for, and that just gets more I'm more broad every day. So I think just being able to be notified about some of those little things, although seems cumbersome, but can be really important depending on who you're going to give that drug to. I know it's in their bones to want to say, well, our drug sister drug to this one, and this is why we're better than them. But I feel like I would like to see a little bit more about but oh, by the way, we did have these issues, but they're not really very good about detailing that for you, with so
Diane Cox:many drugs on the market now, I mean, especially the patients that you treat, it seems to be pretty broad of a population. With so many drugs, what are the ways that physicians and yourself would kind of narrow down the various drugs for a particular application?
Unknown:Yeah, that's a great question. I think a lot of it boils down to, you know, what you get comfortable using, in, I'd say a lot of it comes down to like training. So you'll see people who have trained this way. And so they tend to use these medications or trained here, so they tend to use these. And then it boils down to insurance coverage. A lot of my population has Medicare and and like a Medicare Supplement. And in that sense, I'm kind of at their, you know, mercy of what my drug choices are, and you're dealing with people who are in a fixed income. So as much as I want to use that new like brand new fancy drug that might work best for this patient, it's just simply not an option A lot of times, so you get excited when you get to use some of those newer drugs on people, because they do have really good efficacy data. But unfortunately, they're, they're not within reach of a good chunk of the population.
Diane Cox:That's unfortunate. And interesting. I know that when I'm at the doctor's, and I am, you know, sitting there waiting for whatever the outcome might be, they're oftentimes kind of looking through some database, I don't know what it is, or what it's called. In those databases, or whether you're searching for a particular drug, or you know, the dosage information to figure out what to prescribe for a particular patient. Is it apparent in those what the adverse effects might be?
Unknown:I think it would depend on Yeah, I mean, there's lots of different places you can go for resources like that. Sometimes you're looking at up to see what kind of dose reduction do I need to do for this patient's kidney function or with their liver dysfunction? You know, can I use this drug or? And to an extent, I mean, there's usually an adverse reaction section. I mean, in most of them if there's a blackbox warning that's listed somewhere if there's, but you kind of have to dig for certain things. I mean, I think in education, you know, in your pharmacology lectures, you cover kind of the big hitters side effects like Stevens Johnson Syndrome, all these like rashes, and really bad, could be potentially lethal. affects, angioedema. So swelling of the mouth and lips and things like that. Those kinds of things, I think get covered pretty quickly, even like in school. So you kind of remember that the other kind of little things, different types of weird anemias that can show up in renal failure, or pancreatitis, they kind of get a little muddy, you can find it but it's not always real visible. Yeah.
Diane Cox:Okay. I've actually kind of always wondered that. So thank you.
Unknown:Yeah, I mean, we're usually just, I mean, I'd say like, I appreciate the humility of somebody who will look something up in front of me, because it makes me feel safer, at least on my end, because working in medicine, I know how broad it can be. And so I want them to know what they're what I want to know what they're doing is right? And is the right dose. And, and I think my patients appreciate that too. But because there's just so much to cover anymore. There's so many drugs, so many, so many that I mean, like even every year, I'm like, Well, I've never written for this drug before. So we'll see how this goes. I mean, it's just it, eventually, it happens. But yeah, I think even some of that makes us nervous to not really know, clinically, like you kind of have an anecdotal experience with a lot of drugs like, these are the ones I tend to use, because I've seen the both the best, like clinical outcomes in my clinic when I've used them. But you know, there's not a lot of data in my clinic, per se, to say, Hey, this is the best one. Yeah, that's kind of what I see. Observe anyway. It's
Aaron Harmon:fun talking to you. And I say that because Justin. But because of that curtain, because on the drug development side, you can spend years in a lab developing a drug or device, wherever it may be, but you're not delivering it to the patients. We essentially hand it off, we get approval, we get excited about that. We market it and then it goes to physicians, nurses, TAs, and you guys are the ones that have to know, work with those patients. And you get to know them personally and know their experience and what they're going through. And now it's applying what we've developed on the other side. And I think it's part of the problem with that curtain is I think we lose the view of there's a human on the other side that's got to deal with cost deal with side effects, or try to weigh out those risks and whatever else maybe
Unknown:it can definitely occasionally be a hard sell for a patient. I think like in particular, I deal a lot with like osteoporosis and one of the major like classified side effects here that is called osteonecrosis of the jaw. Nobody wants that. Right. But like, you kind of have a due diligence to tell your patient about that, even though it's super, super unlikely. But then it definitely I've had many people are like, well, I don't know if I want that then. And it's like, the risk of them falling and breaking something is probably much, much higher than this random side effect that it's, you know, it's been tagged with, but the risk is there, and you have a diligence to provide that information to the patient so they can make an informed choice. It's, it's hard sometimes, though, I mean, I appreciate that it's there. And that we know that it's a possibility, but it definitely can make my job harder. I can't tell you how many times I've had a patient come back from the pharmacy be like, well, I read the insert from the medication. And there's just too many side effects. And I don't want to take it, and you can't force them. So
Aaron Harmon:that is the downside of more information. Because back in the thalidomide era, you wouldn't have had any of that it would have been here, try this out. And
Unknown:in the thalidomide era, I mean, medicine was very different, right? It's a very paternalistic model, we don't really have that anymore. It's a very like, informed choice. Like we give you choices, I want you to know, like all the available information, I want you to make the best choice for you, because I'm not in your body. And I don't live with you every single day. And I want you to make the choice that you know, fits with your life the best. Versus before it was just like, Here's your medicine see later, like, this is what we're doing today. Yeah. And I still, like encounter little old ladies who really struggle with making a decision. They're like, I don't know, what do you want to do? And I'm like, well, let's just do this, that and like, they need you to make that decision. But most people in our age group are familiar with being able to make that choice for themselves. So in the thalidomide era, those people didn't know any better. They came in with a complaint. They said Here take this medicine, they complied like a good soldier quote, and, and that was it. There was no Google. Yeah, there was no Google, there was no eye health, there was a drug insert, I doubt you know, none of that stuff their pharmacists are telling them. Oh, by the way, did you talk to your doctor about this? Like, it wasn't that wasn't a thing. So
Diane Cox:yeah, so much trust put into one person that's prescribing that
Unknown:Yeah, absolutely. And nothing in subscribers because they were not wiser either. Exactly.
Aaron Harmon:But I do you think there's still a value in trust. And so if I'm having to choose between a drug on the market that's been through the FDA, and been through all the drug development process that I'm aware of now, I have a lot more confidence, knowing that it will do what it's supposed to do. And if there is risks, I'll be aware of what those risks are, where if I'm getting something that has not been through that process, you're just guessing it's gonna function at all right? Do you think what happened with thalidomide could happen again,
Diane Cox:I think something like the thalidomide accident or that solidified event could happen again. But I think the the chances are a lot lower given that there are so many more controls that have been put in place since that time. And so there have been all kinds of various studies that need to be performed, even before you take a drug to two human beings for a clinical study. And the fact that you have to do all of this in laboratory testing, in vivo testing on animals before you can take them to humans. I think we weed out quite a bit through that process. So while I don't think we can comprehensively cover every scenario, everybody's genetic makeup that might have some interaction with a drug. Everything possible in the world, I think the chances are much lower. And I think things are getting weeded out that way through the controls that have been put in place since a little mine.
Aaron Harmon:Well, thanks for being with us, Justin.
Unknown:Hey, this one. Great, thanks for inviting me. Yeah,
Diane Cox:thank you so much. I learned a lot from your perspective. Great. Glad to hear you answering my question.
Aaron Harmon:And stay tuned for another exciting episode of Inside Out quality.
Diane Cox:We hope you enjoyed this episode. This was brought to you thanks to South Dakota biotech Association. If you have a story you'd like us to explore and share, let us know by visiting www.sd bio.org.
Aaron Harmon:Other resources for quality include the University of South Dakota's biomedical engineering department, where you can find courses on quality systems regulatory affairs, and medical product development. Also, if you live in the Sioux Falls area, check out quit a local Quality Assurance Professionals Network. You can find out more about pivot by clicking on the link on our website to the end and I would like to thank several people, but a few who stand out are Nate peple for a support with audio mixing Barbara Durrell, Christian or support with graphics design and web. And lastly, the support from South Dakota bio